Method and device for anastomoses

ABSTRACT

Provided herein is a device for use in an anastomosis of tissue(s) comprising a biocompatible material and a means of applying radiofrequency energy or electrical energy to generate heat within said biocompatible material. The device also may be used to bond or fuse at two materials where at least one of the material is a tissue. Also provided are methods to anastomose tissue or to bond or to fuse these materials using these devices.

CROSS-REFERENCE TO RELATED APPLICATIONS

This divisional application claims benefit of priority under 35 U.S.C.§120 of nonprovisional application U.S. Ser. No. 10/438,514, filed May15, 2003, which claims benefit of priority under 35 U.S.C. §119(e) ofprovisional U.S. Ser. No. 60/380,817, filed May 15, 2002, now abandoned,the entirely of both of which are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to the fields of biomedicalengineering and surgery. More specifically, the present inventionprovides a device and methods for improving the ease with which anatomicstructures can be anastamosed.

2. Description of the Related Art

There has been an effort recently to identify biocompatible moleculeswhich can be used as a “tissue solder”. Biomolecules such as fibrin,elastin, albumin have been or are used to “glue” tissue-to-tissue. Anumber of patents describe the “activation” of these biomolecules toform “welds” through irradiation, often in the form of laser radiantenergy, but sometimes in the form of ultrasound or radiofrequency waves.The applied energy is believed to denature the molecules, which thenadhere to one-another, or cross-link thereby effecting a union betweenthe tissues.

Over the past fifteen years, a significant amount of scientific researchhas focused on using laser heated “solder” for “welding” tissues such asblood vessels (1-2). Research has been done on laser tissue welding withalbumin solders which are an improvement over conventional sutureclosure because it offers an immediate watertight tissue closure,decreased operative time, especially in microsurgical or laparoscopicapplications, reduced trauma, and elimination of foreign body reactionto sutures, collagen-based plugs and clips. The procedure has beenenhanced with the use of advanced solders, strengthening structures,concurrent cooling, and added growth factors as disclosed, for example,in U.S. Pat. No. 6,221,068.

Use of lasers for tissue welding appeared very promising, however, thetechniques have certain limitations. The laser energy must be manuallydirected by the surgeon which leads to operator variability.Additionally, the radiant energy is not dispersed evenly throughout thetissue. The high energy at the focal point may result in local burns andthe heating effect drops off rapidly at a small distance from the focalpoint. Finally, lasers are expensive and currently cannot beminiaturized easily.

U.S. Pat. No. 5,669,934 describes a method for joining or restructuringtissue by providing a preformed film or sheet of a collagen and/orgelatin material which fuses to tissue upon the application ofcontinuous inert gas beam radiofrequency energy. Similarly, U.S. Pat.No. 5,569,239 describes laying down a layer of energy reactive adhesivematerial along the incision and closing the incision by applying energy,either optical or radiofrequency energy, to the adhesive and surroundingtissue. Further U.S. Pat. No. 5,209,776 and U.S. Pat. No. 5,292,362describe a tissue adhesive that is intended for use principally inconjunction with laser radiant energy to weld severed tissues and/orprosthetic material together.

U.S. Pat. No. 6,110,212 describes the use of elastin and elastin-basedmaterials which are biocompatible and can be used to effect anastomosesand tissue structure sealing upon the application of laser radiantenergy. Both U.S. Patent Application No. 20020045732 and U.S. Pat. No.6,221,335 teach joining living tissues by using laser radiant energy toheat a “solder” consisting of protein, water and a compound whichabsorbs the laser radiant energy, preferably indocyanine green. Thissolder is optionally in the form of a tubular structure which can moreeasily be applied when vascular anastomoses are required. The statedbenefits, inter alia, are the biocompatible and ubiquitous nature ofelastin.

U.S. Pat. No. 6,302,898 describes a device to deliver a sealant andenergy to effect tissue closure. It also discloses pre-treating thetissue with energy in order to make the subsequently applied sealantadhere better. PCT Publication WO 99/65536 describes tissue repair bypre-treating the substantially solid biomolecular solder prior to use.U.S. Pat. No. 5,713,891 discloses the addition of bioactive compounds tothe tissue solder in order to enhance the weld strength or to reducepost-procedure hemorrhage.

U.S. Pat. No. 6,221,068 discloses the importance of minimizing thermaldamage to the tissue to be welded. The method employs pulsed laserirradiation followed by cooling the tissue to nearly the initialtemperature between each heating cycle. U.S. Pat. No. 6,323,037describes the addition of an “energy converter” to the solder mixturesuch that optical energy will be efficiently and preferentially absorbedby the solder which subsequently effects a tissue weld.

Common problems exist throughout the prior art. These include tissuedamage due to uneven heating, unknown and/or uncontrollable thermalhistory, i.e., time-temperature profile, and relatively high cost. It isnotable that a consistent means of treatment and control are desirable.The Code of Federal Regulations, 21 CFR 860.7(e)(1), establishes thatthere is “reasonable assurance that a device is effective when it can bedetermined, based upon valid scientific evidence, that in a significantportion of the target population, the use of the device will provideclinically significant results.” Devices that cannot be shown to provideconsistent results between patients, or even within a patient uponmultiple use, will have minimal utility and may not be approved, ifapproved, for broad use. Beyond devices, it is generally desirable todevelop medical products with critical controls that can deliver preciseresults.

Inductive heating (3) is a non-contact process whereby electricalcurrents are induced in electrically conductive materials (susceptors)by a time-varying magnetic field. Generally, induction heating is anindustrial process often used to weld, harden or braze metal-containingparts in manufacturing where control over the heating process andminimized contact with the workpiece are critical.

Basically, radiofrequency power is coupled to a conducting element, suchas a coil of wire, which serves to set up a magnetic field of aparticular magnitude and spatial extent. The induced currents or Eddycurrents flow in the conductive materials in a layer referred to as theskin depth δ (m), given by:

δ=√(2ρ/μΩ,

where Ω is frequency (rads/s), ρ is resistivity (ohm-m) and μ is thepermeability (Webers/amp/m) which is the product of μo to thepermeability of free space and μr the relative permeability of thematerial.

The magnetic permeability of a material is quantification of the degreeto which it can concentrate magnetic field lines. Note, however, thatthe permeability is not constant in ferromagnetic substances like iron,but depends on the magentic flux and temperature. The skin depth at roomtemperature at 1 MHz electromagnetic radiation in copper is 0.066 mm andin 99.9% iron is 0.016 mm.

The consequence of current flowing is Joule, or I²R, heating. Theskin-depth formula leads to the conclusion that, with increasedfrequency, the skin depth becomes smaller. Thus, higher frequenciesfavor efficient and uniform heating of smaller components. In certainsituations localized heat can also be generated through hysteresislosses or frictional heating, referred to as dielectric hysteresisheating in non-conductors, as the susceptor moves against physicalresistance in the surrounding material. Consideration of Joule heatingalone results in a formula for the power-density P (W/cm³) in theinductively-heated material:

P=4πH²μoμr f M,

where H is the root-mean-square magnetic field intensity (A/m), f isfrequency (Hz), M is a power density transmission factor (unitless)which depends on the physical shape of the heated material and skindepth and diameter of the part to be heated (4-5).

M, which is equal to the product of F and d/d where F is a transmissionfactor and d is the diameter of the part, can be shown to be maximallyabout 0.2 when the object diameter is 3.5 times the skin depth and whencertain other assumptions are made. Thus, for a given frequency there isa diameter for which the power density is a maximum; or equivalent,there is a maximum frequency for heating a part of a certain diameterbelow which heating efficiency drops dramatically and above which littleor no improvement of heating efficiency occurs. It can also be shownthat the power density of inductively heated spheres is much higher thansolid spheres of the same material.

There are only a few examples of the use of inductive heating in themedical literature. The oldest example of use of therapeutic inductiveheating is in hyperthermia of cancer, whereby large metallic “seeds” areinductively heated using a coil external to the body (6). Smaller seedswere used where small biocompatible dextran magnetite particles inmagnetic fluid was used to treat mouse mammary carcinoma by hyperthermia(7). U.S. Patent Application Ser. No. 2002/0183829 describes inductivelyheating stents made of alloys with a high magnetic permeability and lowcurie temperature for the purpose of destroying smooth muscle cells inrestenosing blood vessels. A more recent report described the diagnosticuse of induction heating to heat nanocrystals coupled to DNA in order tolocally denature DNA for the purpose of hydridization (8.)

The literature is deficient in descriptions whereby biomolecules areheated through induction. U.S. Pat. No. 6,348,679 discloses compositionsused in bonding two or more conventional materials where the interposedcomposition consists of a carrier and a susceptor, which may be at leastin part composed of certain proteins. However the applications apply toconventional substrates such as films or wood.

The inventors have recognized an increased need in the art for aprecision device and improved methods of joining tubular, planar orirregular-surfaced tissues to other tissue structures or to dressings.Further, the prior art is deficient in devices and methods forminimally-invasive methods that use electromagnetic energy tocontrollably alter a biocompatible structure thereby making it adhere totissue through molecular alterations and/or mechanical shrinkage. Thepresent invention fulfills this longstanding need and desire in the art.

SUMMARY OF THE INVENTION

The present invention is directed to a device for use in an anastomosisof tissue(s) comprising a biocompatible material and a means of applyingradiofrequency energy or electrical energy to generate heat within thebiocompatible material.

The present invention also is directed to a device for bonding at leasttwo materials, whereby at least one material is a tissue. The devicecomprises a biocompatible material, a means of applying radiofrequencyenergy or electrical energy to generate heat within the biocompatiblematerial and a means of controlling output of the heat generated withinthe biocompatible material conducted to the materials to be bonded orfused.

The present invention is directed further to methods of anastomosis ofat least one tissue or to methods of bonding or fusing at least twomaterials at least one of which is a tissue using the devices describedherein.

Other and further aspects, features, and advantages of the presentinvention will be apparent from the following description of thepresently preferred embodiments of the invention given for the purposeof disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the matter in which the above-recited features, advantages andobjects of the invention, as well as others that will become clear, areattained and can be understood in detail, more particular descriptionsof the invention briefly summarized above may be had by reference tocertain embodiments thereof that are illustrated in the appendeddrawings. These drawings form a part of the specification. It is to benoted, however, that the appended drawings illustrate preferredembodiments of the invention and therefore are not to be consideredlimiting in their scope.

FIG. 1 depicts one embodiment of the device, essentially tubular inshape, used for vascular or tubular structure anastomoses.

FIG. 2 depicts a conductive element positioned within the tubular deviceof FIG. 1.

FIGS. 3A and 3B depict different placement geometries of the conductiveheating elements within the material of tubular device of FIG. 2.

FIG. 4 depicts an inhomogeneous mixture of electric or magnetic fieldabsorbing elements mixed within the material which makes up the tubulardevice.

FIG. 5 depicts cross-sectional view A-A of the device of FIG. 2positioned between two separate ends of a blood vessel which are to beanastomosed.

FIG. 6A depicts the device of FIG. 2 having a second part containingembedded conductors. FIG. 6B depicts the device emplaced around a siteof anastomosis.

FIG. 7 depicts a solenoid-type coil applicator carrying an electricalcurrent and the resultant magnetic field lines.

FIGS. 8A-8D depict three differently shaped flat pancake coils (FIGS.8A-8C) and a containment means for cooling this coil in FIG. 8B (FIG.8D).

FIGS. 9A-9C depict a pancake coil with a non-planar geometry (FIG. 9A)and a conical spiral coil geometry (FIG. 9B). FIG. 9C depicts anapplicator coil suitable for use within tubular structures such as bloodvessels.

FIG. 10A depicts a device that can be used to provide an internalalternating magnetic field that is used to inductively heat abiocompatible fusion material. FIG. 10B depicts the positioning of thedevice around tissues to be anastomosed.

FIG. 11 depicts a coil applicator that can be split thus allowingpositioning of tissue in the interior of the coil.

FIG. 12 depicts an ovine blood vessel anastomosed with an activator,applicator, and fusion composition.

FIG. 13 depicts a histologic section through a blood vessel anastomosedvia the tissue fusion device.

DETAILED DESCRIPTION OF THE INVENTION

In one embodiment of the present invention there is provided a devicefor use in an anastomosis of tissue(s) comprising a biocompatiblematerial and a means of applying radiofrequency energy or electricalenergy to generate heat within the biocompatible material. In allaspects of this embodiment the biocompatible material may conform to thetissue geometry. The biocompatible material may be a liquid, a solid ora semi-solid. Further, in all aspects the device may be usedendoscopically.

In this embodiment the biocompatible material may comprise a protein, abiocompatible polymer, polymeric matrix substance, or a combinationthereof. Examples of a protein is elastin, albumin, fibrin, collagen, orglycoprotein. Representative examples of a polymeric substance ishydrogel, agar or sol-gel. Furthermore the biocompatible material maycomprise a pharmaceutical. The pharmaceutical may be an anti-coagulant,an antithrombotic, an antibiotic, a hormone, a steroidalantiinflammatory agent, a non-steroidal antiinflammatory agent, ananti-viral agent or an anti-fungal agent.

In one aspect of this embodiment the means to apply electrical energy tothe biocompatible material comprises at least one electrode inelectrical contact with the biocompatible material. In a related aspectthe means to apply radiofrequency energy to the biocompatible materialcomprises at least one induction coil proximate to the device where theinduction coil(s) generates an oscillating magnetic field around thedevice. The induction coil(s) may further comprise a cooling meanshaving a cooling fluid and a containment means for the cooling fluid.Examples of a cooling fluid are low viscosity mineral oil or water. Thecontainment means may be a glass envelope containing the cooling fluidand the induction coil(s) or may be copper tubing containing the coolingfluid. Further to this aspect the induction coils may comprise a coatingof a smooth non-adhering material. Examples of a non-adhering materialare teflon, titanium or gold.

In a related aspect the device may further comprise a clamp-likeinstrument having two arms pivotally connected at the center forscissors-like action. The first ends of the arms are attached to theinduction coils. The second ends of the arms function as a handle withwhich to manipulate and position the induction coils proximate to thedevice.

In another aspect of this embodiment the device comprises a means ofcontrolling output of the heat generated within the biocompatiblematerial conducted to the tissues. The heat control means comprises aconductive material in contact with the biocompatible material. Theconductive material has a thermal history such that application ofradiofrequency energy or electrical energy to the conductive materialgenerates an estimable amount of heat. The conductive material may be ametal wire, a metal particle, a ferromagnetic material, a paramagneticmaterial, a conducting polymer, an ionic molecule, a polar molecule or aconducting microsphere. Additionally, the conductive material may be anenergy-absorbing material, said energy-absorbing material comprisingconducting polystyrene microbeads, a colloidal metal, a conductingpolymer, a strongly ionic molecule or a strongly polar molecule.

In another embodiment of the present invention there is provided amethod for performing an anastomosis between at least two tissuescomprising the steps of positioning the device described supra aroundthe tissues such that the tissues simultaneously contact thebiocompatible material of the device and each other, applyingradiofrequency energy or electrical energy to the biocompatible materialand generating heat within the biocompatible material and the tissueswhereby the heating adheres the biocompatible material to the tissues oradheres the tissues to each other thereby anastomosing the tissues. Inthis embodiment adherence of the biocompatible material to the tissuesor of adherence of the tissues results from molecular changes in thebiocompatible material and said tissues. The features of the device,e.g., biocompatible materials, energy sources, induction coils, coolingmeans, heat output control means, conductive elements, orpharmaceuticals, are as described supra.

In yet another embodiment of the present invention there is provided adevice for bonding or fusing at least two materials, whereby at leastone material is tissue, comprising a biocompatible material, a means ofapplying radiofrequency energy or electrical energy to generate heatwithin the biocompatible material and a means of controlling output ofthe heat generated within the biocompatible material conducted to thematerials to be bonded or to be fused. In all aspects of this embodimentthe features of the device, e.g., biocompatible materials, energysources, induction coils, cooling means, heat output control means,conductive elements, or pharmaceuticals, are as described supra.

In still another embodiment of the present invention there is provided amethod for bonding or fusing two materials, whereby at least one istissue, comprising the steps of positioning the device described supraaround the materials whereby the materials simultaneously contact thebiocompatible material of the device and each other, applyingradiofrequency energy or electrical energy to the biocompatiblematerial, generating heat within the biocompatible material; andcontrolling output of the heat to the materials to be bonded or to befused via the heat controlling means of the device such that the outputof heat bonds the biocompatible material to the materials to be bondedor fuses the materials together. In this embodiment bonding of thebiocompatible material to the materials or fusing the materials togetherresults from molecular changes in the biocompatible material and in thematerials. Again the features of the device, e.g., biocompatiblematerials, energy sources, induction coils, cooling means, heat outputcontrol means, conductive elements, or pharmaceuticals, are as describedsupra.

Provided herein are methods for inductively heating non-conventionalsubstrates, i.e. biological materials, in order to cause conformationalchanges that result in unique properties with regard to tissues. Inparticular, methods, devices and compositions are disclosed whereby theprinciples of induction heating are applied to heat biological materialsand cause them to join to one another or to non-biological materials.Particularly, upon inductive heating, proteins, and possibly otherbiomolecules, present in the tissues take part in a fusion process thatallows tissues to adhere to one another. The fusion process may involvethe addition of adhesives between the tissues that could includesusceptors that assist the process of inductive coupling.

Generally, the present invention relates to a device and method forheating a liquid, solid or semi-solid composition to be utilized in thehuman body for bonding tissues or filling defects in tissues. The devicecomprises a source of radiofrequency (RF) energy coupled to anapplicator, which then produces an oscillating magnetic field, and thecomposition which inductively couples with the magnetic field resultingin the transient production of heat substantially within thecomposition. The consequences of heat are molecular changes in thecomposition resulting in fusion with the adjacent tissue. The adjacenttissue also may take part in the fusion process by being altered by thetransient presence of heat.

In the present invention inductive coupling most simply results inheating, via magnetization, particles or other ionic species, eitherhaving non-zero conductivity and magnetic permeability, impregnated in abiocompatible fusion composition or adhesive. The composition may becomprised largely of a protein, e.g., serum albumin, with the additionof a metal such as 300 mesh nickel flakes. The induced electricalcurrents produced in the particles results in heat which then conductsinto the area immediately surrounding the metal, resulting in a“melting” of the adhesive and perhaps the adjacent tissue. Less than asecond later, when the adhesive cools, it forms a bond with the tissue.

The adhesion effect may be a consequence of the proteins in the fusionformulation bonding, perhaps by cross-linking, with other molecules inthe protein formulation as they cool, as well as the proteins in theadhered tissue. This may be considered as a “bridge” between themolecules and a “scaffold” between the tissues. The endogenous proteinsin the tissue also may have been denatured and coagulated due to nearbyheat production which may be critical to the adhesion strength.

It is contemplated that in tissue the temperatures needed to achieve abond range from about 45-85° C. and that the heating times are veryshort since protein denaturation is essentially instantaneous once acritical temperature is achieved. Thus, the powers required for thepresent device and method are far less than those used in commerciallyavailable industrial induction-heating devices which are used forwelding metals and plastics. Accordingly, the present invention can beproduced for a fraction of the cost of commercial devices.

The source of RF energy provides electrical energy to a probe whichcomprises an electrically conducting material, such as copper, wound inthe shape of a solenoid or coil. Other probe shapes may prove moresuitable for particular applications. The conducting material may behollow or may be solid. The probe may be cooled. If the conductingmaterial comprising the probe is hollow, a cooling fluid can becirculated within its lumen. The solid probe material may be positionedwithin a liquid-tight envelope such that coolant, preferably one of lowelectrical permitivity, e.g. mineral oil, can be circulated around it tokeep it from overheating.

The conducting material comprising the probe sets up an oscillatingmagnetic field which inductively couples to a conductive material in thebiocompatible composition when the material is positioned within themagnetic field. Through physical movement of the conducting materialand/or the establishing of eddy currents within the conducting materialor the tissue and/or composition and/or hysteresis losses, heat isproduced. The heat diffuses into the surrounding composition and tissuethereby causing protein denaturation and alteration of surroundingbiomolecules, e.g. lipid melting. This heating results in conformationalchanges in the molecules which effect adherence in the tissues. In asimple case, depending on the protein, denaturation may result in linkswith adjacent molecules thus effecting the bond.

Thus, the present invention provides a tissue-fusion-device (TFD). TheTFD operates by electromagnetically heating the biocompatible fusioncompositions to create tissue bonds. The TFD comprises a fusioncomposition, an applicator and an activator.

Fusion Composition

The materials that comprise the fusion composition must bebiocompatible, able to be inductively heated and able to produce afusion in biomaterials. The fusion composition may comprise abiocompatible polymer, a protein such as albumin, elastin and/orcollagen or polysaccharides, e.g. cellulose, starch, chitosan, alginate,emulsan, or pectin. Examples of biodegradable polymers are polylactide(PLA), polyglycolide (PGA), lactide-glycolide copolymers (PLG),polycaprolactone, lactide-caprolactone copolymers, polyhydroxybutyrate,polyalkylcyanoacrylates, polyanhydrides, and polyorthoesters. Examplesof biocompatible polymers are acrylate polymers and copolymers such asmethyl methacrylate, methacrylic acid, hydroxyalkyl acrylates andmethacrylates, ethylene glycol dimethacrylate, acrylamide, bisacrylamideor cellulose-based polymers, ethylene glycol polymers and copolymers,oxyethylene and oxypropylene polymers, poly(vinyl alcohol),polyvinylacetate, polyvinylpyrrolidone and polyvinylpyridine.Optionally, protein primers, which are substances that exhibit groupsthat can cross-link upon the application of heat, can be added.

Proteins are particularly attractive in tissue bonding applications inthat they typically denature at temperatures less than 100° C.Denaturation can lead to cross-linking with other molecules,particularly proteins, in the immediate environment while the proteinsare still in the denatured state, or upon their renaturation. Additionalmaterials added to the composition formulations may result in greaterflexibility and tensile strength as well as optimum treatment times andtemperatures. The formulations utilize commonly occurring tissue andproteins, such as albumin, collagen, elastin, but may also contain silk,lignin, dextran, or may contain soy-derivatives, poly-glutamic acid,combined with additives such as polyethylene glycol or hydrogel toimprove the rheologic nature of the adhesive.

Optionally, hyaluronic acid can be added to the composition to enhancethe mechanical strength of adhesives, such as is sometimes done in lasertissue welding, or pre-denaturation may take place before application ofthe composition at the treatment site. Other materials, such asfibrinogen or chitin or chitosan, may be added to the composition toprovide hemostasis and/or some degree of immediate adhesion. Materialssuch as calcium phosphate or polymethylmethacrylate, also can be used,most beneficially when boney material is the tissue to be treated.

Additionally, pharmaceuticals, e.g., an anti-coagulant, anantithrombotic, an antibiotic, a hormone, a steroidal anti-inflammatoryagent, a non-steroidal anti-inflammatory agent, an anti-viral agent oran anti-fungal agent, may be beneficially added to the composition inorder to provide some desirable pharmacologic event.

Optionally, destabilizing/stabilizing agents, e.g. alcohol, can be addedas they have been shown to alter the denaturation temperature. Forexample, an increase in the concentraion of NaCl, referred to as“salting-in” proteins, can increase the denaturation temperature ofglobulin, while an increase in the concentraion of NaClO₄, or“salting-out”, reduces the denaturation temperature (9). When proteinsare exposed to either liquid-air or liquid-liquid interfaces,denaturation can occur because the protein comes into contact with ahydrophobic environment. If allowed to remain at this interface for aperiod of time, proteins tend to unfold and to position hydrophobicgroups in the hydrophobic layer while maintaining as much charge aspossible in the aqueous layer. Thus, by ultrasonically adding bubbles,e.g., of gas, to the composition will serve to lower the denaturationpoint of the mixture.

The conductive materials that can be inductively heated are added to thecomposition in amounts typically no more than 10% by weight, althoughother concentrations can be used, but not limited to 0.1-25%. Thematerial may include salts or other ionic species, or metals of variablesize. For example, nanometer sized particles to macroscopic sizedparticles up to 1 mm in size can serve as effective susceptors.Alternatively, the conductive material may take of the form of a fineconductive lattice or mesh, such as available from Alfa Aesar Inc (WardHill, Mass.).

Examples of conductive materials that may be useful by themselves or inalloys are, although not limited to, tantalum, niobium, zirconium,titanium, and platinum which are some of the most biocompatibleelements. Additional conductive materials may be phynox, which is analloy of cobalt, chromium, iron, nickel, molybdenum, palladium/cobaltalloy, magnetite, nitinol, nitinol-titanium alloy, titanium, whichoptionally may be alloyed with aluminum and vanadium at 6% Al and 4% V,tantalum, zirconium, aluminum oxide, nitonol which is a shape memoryalloy, cobalt, which optionally may be alloyed with chromium, molybdenumand nickel, or, optionally, 96% Co/28% Cr/6% Mo alloy, iron, nickel,gold, palladium, and stainless steel, e.g., biocompatible type 316L. Theconductive materials may take the shape of a mesh, fibers, macroscopicand solid materials, flakes or powder. The conductive materials may beanodized and may further be encapsulated in materials such as liposomes,compounds such as calcium phosphate, polystyrene microspheres,pharmaceuticals, hydrogels, or teflon. These encapsulating materials mayminimize the chance of an immune response to the conductor, may induct adesirable pharmacologic event, or may enhance the inductive coupling tothe activating magnetic field.

The rheology of the fusion composition can be important. For example,producing the composition in a low-viscosity liquid form would allowinjection through a cylindrical pathway such as a trochar orworking-channel of an endoscope. A higher viscosity material can beapplied to a tissue and will stay in place prior to activation. A solidformulation could be shaped, for example, as a tube, which could be thembe positioned in a tubular anatomical structur, e.g. blood vessel orureter, thus providing mechanical support prior to activation.

Other shapes may be more appropriate for different procedures. Forexample, a flat-sheet of composition would be suitable for sealing alarge area of skin or soft-tissue, while a solid cylinder could be mostappropriate for placement in the cavity left behind after a cannula isextracted. A porous structure of the fusion formulation might bebeneficial for the subsequent in-growth of cells. It is conceivable thatthe conductive material itself, when distributed throughout thetreatment area, would employ the endogenous proteins in productionadhesion thus precluding the use of an external protein in theformulation.

Cross-linked polymers are quite insoluble, but they can be swollen todifferent degrees depending on their cross-linking. Swelling can beinitiated by changes in temperature, pH, solvent type, ionic strength,light intensity, pressure, and electromagnetic fields. Hydrogels can bemade biologically inert or biodegradable and are easily derivatized,particularly with enzymes. They can be grafted or bonded onto othermaterials, even living tissue.

The equilibrium swelling degree or sorption capacity, i.e., swollenvolume/dry volume, is one defining property of a hydrogel. Dependingupon the formulation, the swelling degree can be widely varied as canthe sorption rate, which is roughly proportional to the equilibriumswelling degree. Permeability to water, drugs, proteins, and otherbiomolecules can be varied over wide ranges depending upon the swellingdegree or water content. Hydrogels may be a useful optional addition tothe fusion formulation as they give it different thermal and mechanicalproperties and also allow for the incorporation of a pharmaceuticalwhich can ultimately diffuse out of the fusion composition.

The biocompatible fusion composition may optionally have differentadditives depending on the material to which adhesion is required. Forexample, the material used in a vascular graft is typically manufacturedfrom polytetrafluoroethylene (PTFE). The fusion composition could beprepared to preferentially adhere to PTFE. In one example, gelatinizedPTFE, when used as one of the components of the fusion composition,could adhere to the PTFE in situ, thus effecting the desired result.This aspect is particularly important as it can result in the bonding ofimplantable materials, so they are stabilized, sealed or have materialsbonded to them.

Furthermore, the fusion composition may incorporate a support lattice,such as can be made from poly(DL-lactide-co-glycolactide), silk or aninert material, such as teflon or nylon, or a conductive material suchas fine stainless steel mesh. The support material would allow for thefusion composition to be formed into a particular geometric shapesuitable for application to a particular anatomical structure.

For use in vascular anastomoses a preferable shape for thebiocompatiblefusion material is tubular as shown in FIG. 1. The tube hasan outer surface and an inner surface and a first open end and a secondopen end. The open ends are in parallel and have a diameter equal to adiameter across the inner surface of the tube.

The tubular fusion composition may further comprise a conductivematerial or conductive element, such as a metal wire, that is helicallyshaped and uniformly coiled within the biocompatible material (FIGS. 2,3A). Alternatively, the conductive element may be distributedasymmetrically within the biocompatible fusion material so that theelement is positioned where heat distribution is preferable (FIG. 3B).The conductive element may optionally be positioned on the insidesurface, the outside surface or on both surfaces of the tubular devicefor heat transfer to the tissue that is in contact with thebiocompatible material in order to effect a bond. Application ofelectrical energy to each end of the helical conductive element by, forexample, an electrode or induction of an alternating magnetic fieldaround the device heats the conductive element to a critical temperaturewhereby the physical changes in the biocompatible material take place.

The tubular fusion composition of the present invention may also containan energy-absorbing material in addition to the biocompatible materialthat efficiently, as compared to human tissue, absorbs electromagneticenergy. Such energy-absorbing material is analogous to the conductiveelements but are more particulate, i.e., not as macroscopic in structureas the conductive elements may be. The distribution of theenergy-absorbing material may be such that more incident electromagneticenergy is absorbed where it is desired to produce more heat. Thisdistribution is similar to the asymmetrical distribution of theconducting elements (FIG. 4). The energy-absorbing material may be, forexample, conducting polystyrene microbeads, magnetic or metal-containingmicrobeads or nano-particles, colloidal metals, conducting polymers, orstrongly ionic or polar molecules.

The tubular fusion material of the present invention is used to jointubular or approximately cylindrical anatomic structures, such asvascular vessels, to other tubular structures or to non-tubularstructures. For example, in the situation where a patient is to undergominimally invasive coronary artery bypass graft surgery (CABG), asurgeon gains endoscopic access to the obstructed cardiac blood vessel,whereupon dissection of the vessel at each end of the obstructionoccurs. An appropriate length of a suitable bypass graft material,either man-made or a transplant, is positioned between the dissections.The first end of the tubular fusion material is fitted over the end ofthe healthy vessel in situ and the second end of the tubular fusionmaterial is fitted over the bypass graft. The ends of the vessel and ofthe graft material are positioned to contact each other and a bond iseffected between the vessel and the graft by applying RF to generate anexternal oscillating magnetic field or by applying a brief pulse ofelectrical energy to each end of the conductive element in thecylindrical device.

Alternatively, the ends of the healthy vessel and of the graft tissueare everted around the outer edge of the tubular fusion material. Inthis instance the tubular device may have an appended second partcomprising the biocompatible fusion material.

The appendage may also comprise the conducting element or the energyabsorbing material embedded within the tubular material.

The appendage to the tubular material is attached to the tubularmaterial at one end, extends out and over the tubular material to adistance beyond the first open end of the tubular material and is openat this same end as the tubular fusion material. The diameter across theinner surface at the open end of the appendage is equal to the innerdiameter of the tube (FIG. 6A). Thus, when the tubular material isemplaced so that the healthy vessel and the graft tissue or material areeverted around the first open end, the appendage fits over the outersurface of the vessel to be anastomosed and is in contact with thevessel along that outer surface (FIG. 6B).

This allows the outer surface of the vessel to be heated when a briefelectrical pulse is applied to the conductive element. The pulse may bein the form of a unipolar or bipolar pulse of direct current, whichdepending on the material that makes up the conductive element, may beas small as a few volts and milliamps. The temporal extent of the pulsecan be as short as about a few microseconds and multiple pulses may berequired to obtain the desired effect. Longer pulses may also be used,however, an overproduction of heat might induce undesirable damage tothe proximal tissue. Generally, the pulse should be brief enough and ofenough magnitude to induce heating of the conductive element so that thethreshold for a particular molecular change of the biocompatiblematerial and of the outer surface of the vessel and bypass graft isexceeded. A temperature contemplated for such a molecular change isabout 85° C.

Applicator

Applicator geometry greatly affects the distribution of the resultantelectromagnetic field. Several different designs for the applicator arepossible. The most efficacious design depends on the procedure for whichthe applicator is intended.

For induction heating, a coil of wire may be connected to an activatorin order to produce a strong and uniform magnetic field along thelong-axis of the coil (FIG. 7) and is most suitable for inductivelyheating materials positioned within the turns of the coil.Alternatively, the magnetic field can be externalized from the interiorof the coil with the use of a core material, such as used intransformers. The core material may be a magnetic material and,optionally, a powdered magnetic material so that heat production in thecore is minimized.

Other applicator designs allow for a relatively strong magnetic field tobe produced exterior to the wire or tubing. For example, the designsshown in FIGS. 8A-8C are three examples of applicators whereupon thefield is produced above or below the plane of the conductor. In FIG. 8A,the strongest field is produced below each separate coil while in FIGS.8B and 8C, the strongest field is produced in a single position belowthe coil.

The applicator also may be bent into a particular shape, as demonstratedin FIGS. 9A-9B, whereupon the distance between the material to be heatedand the conductor that makes up the applicator is minimized. Thisprovides for an efficient use of energy. Additionally, the applicatormay be shaped to be symmetric around an axis and is designed for use ina hollow anatomical structure, such as a blood vessel (FIG. 9C).

Optionally, a ferromagnetic material, e.g. pole-piece, may be partiallypositioned in the magnetic field produced by the applicator therebyallowing the field to be transferred to the end of the pole-piece thusproducing concentration of the field lines and providing greateraccessibility to the field. At high frequencies, it may be beneficialfor this pole piece to be made substantially from powdered ferromagneticmaterials in order to minimize undesirable heating in the pole pieceitself.

If required, the coil can be cooled by encapsulating it in a glassenvelope through which a cooling fluid, such as low viscosity mineraloil, can be circulated. Cooling is enhanced by using a hollow tubing,such as copper, through which a cooling fluid such as water can becirculated. The advantage therein is that the dielectric property of thecooling fluid is irrelevent because it is contained within theconducting coils and not on the outside where it would be inductivelycoupled to the produced magnetic field. Optionally, the tubing materialmay be coated in a biocompatible non-stick material, such as teflon, sothat heated tissue will not adhere to the applicator.

An oscillating magnetic field may be applied using an instrument havingtwo separate coils attached independently to the ends of a clamp-likeextension (FIG. 10A). The coils can be coated in a smooth non-adheringmaterial which comprises, for example, teflon, titanium or gold. Usingthe scissors-like action of the clamp, the instrument is positionedaround and proximal to the biocompatible fusion material such as aroundthe tubular configuration used for vascular anastomoses (FIG. 10B). Thecoils can be attached to a radiofrequency power supply or activator thatproduces the oscillating magnetic field within the coils. Alternatively,a single coil may be made in such a way that it can be opened up thusallowing a tissue, such as a blood vessel, to be positioned within thecoil which then closes and completes the circuit (FIG. 11).

Activator

The power-supply can produce radiofrequency energy with a power in therange 10-10,000 W and may typically operate at frequencies of 100 kHz to5 GHz. The best operating frequency depends, inter alia, on the natureof the fusion composition to be heated, the geometry of the tissue to befused or the cavity to be filled and regulatory criteria. The outputimpedance of the power-supply is preferably matched to the inputimpedance of the applicator.

The power-supply has several safety features incorporated. For example,the output is optionally low voltage, i.e., <50V, and the device isshielded for emitted or received electromagnetic-interference. Thermalswitches are incorporated within the device to shut it down ifoverheating occurs. Fast breakers quickly cut off the output if apower-output transient occurs. Multiple interlocks are incorporated intothe device which prevent running the device with the cover removed. Afoot pedal is optionally incorporated in order to minimize thepossibility of unintentional activation of the device.

The tissue fusion devices of the present invention are useful fortreating tissue in an individual or animal to effect a fusion or bondbetween two or more elements of tissue. The TFD utilizes at least onebiocompatible material comprising a substance which functions as abonding agent between the tissue and the material(s) interspersed with aconductive element, the activator and applicators described herein and ameans to control the amplitude and persistence time of the field. Themethod may be used to effect a sealing of a sinus in tissue whereby thebiocompatible material functions as a sealing agent.

The tissue fusion devices may be used to effect a fusion between atissue and at least one material. The TFD is placed on the tissue of theindividual whereupon high frequency electrical energy is delivered tothe conductive element within the device or inductively heating theconducting element within the device. The TFD is monitored to controlthe extent of the weld between the tissue and the material(s).

Control may be exerted by direct feedback monitoring of heat generationor by prediction and measurement of the magnetization of the compositionover time with regard to its volume and mass. This feedback may arisefrom measurements of impedance changes in the applicator, as the tissuebecomes part of the circuit during treatment, or devices such asthermocouples or infrared thermometers can be employed. A second orderof control may be exerted through the use of ferromagnetic metals andalloys as susceptors that remain magnetized until reaching a criticaltemperature, i.e., the Curie temperature, whereupon they cease to bemagnetic.

As described below, the invention provides a number of therapeuticadvantages and uses, however such advantages and uses are not limited bysuch description. Embodiments of the present invention are betterillustrated with reference to the Figure(s), however, such reference isnot meant to limit the present invention in any fashion. The embodimentsand variations described in detail herein are to be interpreted by theappended claims and equivalents thereof.

FIG. 1 depicts a device 10 having an essentially tubular structure whichis formed from preferably a biocompatible material 15. The tubulardevice 10 has an outer surface 12 and an inner surface 13 and has afirst open end 14 a and a second open end 14 b.

In FIG. 2 and with continued reference to FIG. 1, a conducting element20 is incorporated within the material 15 comprising the tubular device10. The conducting element 20 is helically shaped and is embeddedbetween the outer 12 and inner 13 surfaces of the tubular device 10 andcoils from a first end 21 a at the first open end 14 a of the device 10to a second end 21 b at the second open end 14 b of the device 10.

With continued reference to FIG. 2, FIGS. 3A and 3B depict across-section of the tubular device 10 with alternate placements of theconductive element(s) 20 within the biocompatible material 15. Theconductive elements 20 can be placed symmetrically throughout thetubular device 10 for uniform heating of the biocompatible material 15of the device 10 as demonstrated in FIG. 3A. Alternatively, theconductive elements 20 can be embedded asymmetrically within thebiocompatible material 15 to provide more heat where it is needed, suchas at the site to be anastomosed as shown in FIG. 3B.

With continued reference to FIGS. 3A and 3B, FIG. 4 depicts across-section of the tubular device 10 having an electromagneticenergy-absorbing material 25, more particulate in structure than theconducting elements 20, that is distributed within the biocompatiblematerial 15. Distribution of the energy-absorbing material 25 is similarto that of the asymmetrical placement of the conducting element 20.

With further reference to FIG. 2, FIG. 5 depicts a cross-section of thedevice 10 as it is emplaced. The tubular device 10 containing theconducting element 20 or energy-absorbing material 25 is fitted over thegraft tissue 30 such that the outer surface 36 of the graft tissue 30 isin contact with the inner surface 13 of the tubular device 10. The graft30 is positioned so that an open end 33 of the graft 30 is evertedaround the first open end 14 a of the device 10 such that the outersurface 31 of the everted end 33 of the graft 30 is in contact with theouter surface 12 of the tubular device 10. The device 10 containing theeverted graft tissue 30 is placed within the opening 38 of the healthyvessel 35 to be anastomosed such that the inner surface 37 of the vessel35 is in contact with both the everted end 33 of the graft tissue 30 andthe outer surface 11 of the tubular device 10. Application of anelectric current to the conducting elements 20 or the energy-absorbingmaterial 25 would heat the biocompatible material 15 and effect amolecular change within the material 15 and within the graft tissue 30and the healthy vessel 35 such that cooling of the biocompatiblematerial 15 results in an anastomosis of the tissues 30, 35.

Continuing to refer to FIGS. 2 and 5, FIG. 6 depicts a cross-sectionalview of an alternate structure and emplacement for the tubular device10. The device 10 has an appendage part 11 surrounding the tubulardevice 10. The appended part 11 has an outer surface 16 and an innersurface 17 and has a first open end 18 and a second end 19 which isattached to the outer surface 12 of the tubular device 10 at the secondopen end 14 b of the tubular device 10. The appendage 11 extends out andover the tubular device 10 from the attached second end 19 toward thefirst open end 14 a of the tubular device 10. The inner diameter of thefirst open end 18 of the appendage 11 and the inner diameter of thefirst open end 14 a of the tubular device 10 are about equal. The firstopen end 18 of the appendage 11 is at a distance from the first open end14 a of the tubular device 10 sufficient to accommodate the graft tissue30 and the healthy vessel 35 everted around the first open ends 14 a, 18of the tubular device 10 and the appendage 11. The appendage 11 maycomprise the conductive element 20 or the energy-absorbing material 25distributed within the material 15 of the tubular device 10 as depictedin FIG. 3A, 3B or 4.

As shown in the cross-sectional view depicted in FIG. 6B, when thetubular device 10 is emplaced as demonstrated in FIG. 5, the open end 38of the healthy vessel 35 is everted around the open first end 18 of theappendage 11 such that the inner surface 17 of the appendage 11 is incontact with the outer surface 36 of the healthy vessel 35. As in FIG.5, application of an electric current to the conducting elements 20 orthe energy-absorbing material 25 would heat the biocompatible material15 in both the tubular device 10 and the appendage 11 and effect amolecular change within the material 15 and within the graft tissue 30and the healthy vessel 35 such that cooling of the biocompatiblematerial 15 results in an anastomosis of the tissues 30, 35.

FIG. 7 depicts an applicator 100 having an essentially solenoid coilstructure 110 which is formed with an interior cylindrical zone 112. Thesolenoid coil 110 has electrical connectors 115 a,b. The magnetic fieldlines 118 produced when an electrical current is passed through theelectrical connectors 115 a,b is shown. While the greatest magneticintensity H (A/m) occurs within the applicator, a weaker magnetic fieldoccurs at the ends and outside of the solenoid 110.

FIGS. 8A-8C depict substantially flat applicator coils for activating inother anatomical geometries. FIG. 8A shows a “butterfly coil” 120 withelectrical connectors 125 a,b. FIGS. 8B-8C show a spiral coils 130 withelectrical connectors 135 a,b and spiral coil 140 with electricalconnectors 145 a,b, respectively. Each coil 120, 130, 140 produces amagnetic field with a particular geometric shape. Coil 120 produces atwo-lobed shaped field above and below the flat plane of the coil (notshown). With the addition of a material, such as mumetal, it is possibleto shield the superior surface of the coil if no magnetic field isdesired above the coil. FIG. 8D depicts the spiral coil 140 positionedwithin a cooling fluid envelope 146, optionally made of glass, throughwhich cooling fluid can be circulated by introducing and extractingcooling fluid through the apertures 147 a,b. Optionally, the coolingfluid can be circulated through the spiral coil 140 itself by beingintroduced and extracted through the electrical connectors 145 b and 145a.

In FIG. 9A and with continued reference to FIG. 10B, a non-planar coilapplicator 150 is illustrated. The coil 150 with electrical connectors155 a,b is similar to coil 130 in FIG. 10B, but each half 153 a, 153 bof coil 150 is bent towards the centerline 152, thus increasing themagnetic field intensity H at a position within a volume containedwithin the bent coil 150. FIG. 9B depicts a coil 160 with electricalconnectors 165 a,b which is in the form of a conical spiral with axis ofsymmetry 162. FIG. 9C shows a fusion applicator coil 170 with electricalconnectors 175 a,b which is symmetrical around axis 172 and which isdesigned for use in a hollow anatomical structure, such as a bloodvessel (not shown).

FIG. 10A depicts a clamp-like instrument 60 with which to apply anexternal oscillating magnetic field. The instrument 60 comprises ascissors-like extension having two arms 61 a,b pivotally connected atthe center 62. The arms 61 a,b have a first end 63 a,b attached to acoil 65 a,b and have a second end 64 a,b comprising a gripping means.The coils 65 a,b form an essentially planar structure each having anouter surface 66 a,b and an inner surface 67 a,b and are each attachedto a first end 63 a,b of the arms 61 a,b so that the inner surfaces 67a,b of the coils 65 a,b are juxtaposed essentially horizontally and inparallel to each other. The pivotal action of the arms 61 a,b increasesor decreases the distance between the inner surfaces 67 a,b of theinductive coils 65 a,b such that the coils 65 a,b may be positionedaround a site of anastomosis. The inductive coils 65 a,b are attached toa radiofrequency source (not shown).

FIG. 10B depicts the positioning of the instrument 60 around a site tobe anastomosed where the tubular device 10 is emplaced as shown in FIG.5. The inductive coils 65 a,b are designed such that when positionedaround an anastomosis site the inner surfaces 67 a,b of the coils 65 a,bare in contact with the outer surface 36 of the healthy vessel 35 at thepoint where the healthy vessel 35 is everted around the graft tissue 30and the tubular device 10. Application of radiofrequency to the coils 65a,b induces a magnetic field which heats the conducting elements 20 orthe energy-absorbing material 25 in the biocompatible material 15 of thetubular device 10 and, as in FIG. 5, effect a molecular change withinthe material 15 and within the graft tissue 30 and the healthy vessel 35such that cooling of the biocompatible material 15 results in ananastomosis of the tissues 30, 35.

FIG. 11, with continued reference to FIGS. 7 and 10A, depicts asolenoid-type applicator coil 180 constructed such that it can beopened, thus allowing the positioning of an anatomical structure (notshown) within the interior cylindrical zone. The coil halves 182 a,b areattached to a clamping device 60 as depicted in FIG. 10A. When thecoil-halves 182 a,b are closed, they establish electrical contact and sothe resulting intensity H is consistent with the field 118 shown in FIG.7. The clamping device 60 is electrically isolated from the coil 180 byinsulators 187 a,b, placed at the arms 61 a,b of the clamping device 60.Power is conducted to the coil halves 182 a,b with electrical connectors185 a,b.

FIG. 12 depicts the visible fusion 410 of a vascular vessel 400.

FIG. 13, with reference to FIG. 12, shows a histological section of thevascular vessel 400 with metallic particles 430 and 440 at the interface410 between the two overlapping sections.

The following examples are given for the purpose of illustrating variousembodiments of the invention and are not meant to limit the presentinvention in any fashion.

Example 1 Heating of Test Metal

The tissue fusion activator device constructed operates at a frequencyof about 650 kHz and has an output of approximately 210 W. At or nearthis frequency, the skin depth in tissue for canine skeletal muscle at 1MHz (10) is about 205 cm, while for nickel it is 160 p.m. Thus, nosignificant heating of tissue occurs as a direct result of the field.Heating only occurs in close proximity to the fusion composition. Twosolenoid-type applicator designs were used, and were made up of 200turns of solid copper wire, 32 and 22 G, thus resulting in a coilapproximately 2.86 cm in diameter and 0.95 cm in width. The bore of thecoil was about 0.5 cm. The coils were encapsulated in a Pyrex sleeve,through which low-viscosity mineral oil (Sigma-Aldrich Inc., St. Louis,Mo.) was circulated as a coolant. In each of these coils, the magneticintensity at the center of the coil is calculated to be greater than10,000 A/m, while at approximately 0.5 cm from a single coil face theintensity is calculated to be maximally 160 A/m.

The blade of a small screwdriver (Craftsman Model 41541, 3.15 mmdiameter) was positioned within the bore of the coils. After 1-5seconds, the screwdriver was extracted and the blade was brought intobrief contact with the skin of the hand. It was immediately apparentthat significant heating had taken place in the blade of thescrewdriver.

Example 2 Heating and Coagulating of Test Fusion Formulation

Fusion formulations were made of 50-75% (w/v) albumin (Bovine serum, orovalbumin; Sigma-Aldrich, St. Louis, Mo.) in saline with a metaladditive of 5% or 10% (w/v) nickel flake (average particle size=50micron, Alfa Aesar, Ward Hill, Mass.) or 10% iron filings (particlesize<30 microns; Edmund Scientific, Tonawanda, N.Y.)). Aliquots ofapproximately 1 ml of the fusion composition was positioned inthin-walled glass tubes with a diameter of about 4 mm. The tube was thenpositioned in the bore of the applicator. The device was energized for aperiod of 20-30 seconds. Evidence of denaturation and coagulation wasascertained visually as the material changed color. This was confirmedby probing the composition with a needle, which demonstrated evidence ofincreased viscosity or stiffness. The composition coagulated with allcombinations of applicator and composition. Compositions with more metalor iron versus nickel heated at different rates.

Example 3 Fusion of Vascular Tissue

A series of experiments were performed using donated carotid, femoraland brachial artery samples harvested from sheep. The samples wererinsed in physiologic saline, placed in wet gauze, and frozen at −20° C.before use. After thawing, each sample was bisected lengthwise with ascalpel. The fusion formulation of 5% Ni and 50% albumin was placedaround the periphery of one end of a bisected sample, i.e. on theadventitia, and the end of the other bisected sample was manuallydilated and pulled over the fusion formulation so that there was anoverlap of a few millimeters. A glass rod was positioned within theintima of the two vessels as a support to hold the tissue in place. Thesample was then positioned between the faces of two opposingsolenoid-type applicators, and the sample exposed to approximately 210 Wof power for about 30 seconds.

As seen in FIG. 12, fusion of the vessel 400 was visually apparent 410,and the fused tissue could not be teased apart with forceps withoutdamage to the tissue. There was no visual evidence of burning. Testswere repeated five times with equivalent results. The vessels wereplaced in 10% formalin, sectioned transversely, or perpendicular to thelong-axis of the vessel, across the fused area and submitted forhistological preparation and staining with hematoxylin-eosin. A samplehistologic section is presented in FIG. 13 which shows the vessel 400and the presence of metallic particles 430 and 440 at the interfacebetween the two overlapping sections.

The following references are cited herein:

-   1. Bass, L S and Treat, M R. Laser Surg. Med. 17, 315-349 (1995).-   2. Freid, N M and Walsh, J T. Lasers Surg. Med. 27, 55-65 (2000).-   3. Davies E J. Conduction and Induction Heating. Inst. Elect. Engs.    and P. Peregrinus:London (1990).-   4. Orfeuil M. Electric Process Heating:    Technologies/Equipment/Applications. Battelle Press: Columbus Ohio    (1987).-   5. Zinn S, and Semiatin S L. Elements of Induction Heating-Design,    Control and Applications, Electric Power Research Institute: Palo    Alto, Calif. (1988).-   6. Stauffer P R, Cetas R C and Jones R C. IEEE Trans. Biomed. Eng.    BME-31, 235-251 (1984).-   7. Jordan A. et al, Int. J. Hyperthermia. 13(6):587-605 (1997).-   8. Hamad-Schifferli K, Schwartz J J, Santos A T, Zhang S and    Jacobson J M., Nature 415, 152-155 (2002).-   9. Damodaran S. Int. J. Biologic. Macromolec. 11, pp. 2-8 (1989).-   10. Francis Duck. Physical Properties of Tissue-A Comprehensive    Reference Book. Academic Press: NY (1990).

Any patents or publications mentioned in this specification areindicative of the levels of those skilled in the art to which theinvention pertains. These patents and publications are hereinincorporated by reference to the same extent as if each individualpublication was incorporated specifically and individually by reference.

One skilled in the art will readily appreciate that the presentinvention is well adapted to carry out the objects and obtain the endsand advantages mentioned, as well as those inherent therein. It will beapparent to those skilled in the art that various modifications andvariations can be made in practicing the present invention withoutdeparting from the spirit or scope of the invention. Changes therein andother uses will occur to those skilled in the art which are encompassedwithin the spirit of the invention as defined by the scope of theclaims.

1. A device for creating an anastomosis of tissue(s) comprising: afusable biocompatible material; at least one induction coil disposed inrelation to the biocompatible material; and means for controlling outputof the heat generated within the biocompatible material conducted to thetissues via a radiofrequency-induced oscillating magnetic field aroundthe induction coil(s)
 2. The device of claim 1, wherein thebiocompatible material conforms to tissue geometry such that saidmaterial is effective to bond or to fuse at least two materials of whichat least one material is a tissue.
 3. The device of claim 1, whereinsaid biocompatible material is a liquid, a solid or a semi-solid.
 4. Thedevice of claim 1, wherein said biocompatible material comprises aprotein, a biocompatible polymer, polymeric matrix substance, or acombination thereof.
 5. The device of claim 4, wherein said protein iselastin, albumin, fibrin, collagen, or glycoprotein.
 6. The device ofclaim 4, wherein said polymeric substance is hydrogel, agar or sol-gel.7. The device of claim 4, wherein said biocompatible material furthercomprises a pharmaceutical.
 8. The device of claim 7, wherein saidpharmaceutical is an anti-coagulant, an antithrombotic, an antibiotic, ahormone, a steroidal antiinflammatory agent, a non-steroidalantiinflammatory agent, an anti-viral agent or an anti-fungal agent. 9.The device of claim 1, wherein the at least one induction coil isadapted to generate an oscillating magnetic field around the device. 10.The device of claim 9, further comprising a means of cooling saidinduction coil(s), said cooling means comprising: a cooling fluid; and acontainment means for said cooling fluid.
 11. The device of claim 10,wherein said cooling fluid is low viscosity mineral oil or water. 12.The device of claim 10, wherein said containment means is a glassenvelope containing said cooling fluid and said induction coil(s) orcopper tubing containing said cooling fluid.
 13. The device of claim 9,further comprising a clamp-like instrument, said instrument comprising:a first arm and a second arm, said first and second arms pivotallyconnected at the center, said first and second arms having a first endattached to said induction coils and a second end for manipulating andplacing said induction coils proximate to said biocompatible material.14. The device of claim 9, wherein said induction coils further comprisea coating of a smooth non-adhering material.
 15. The device of claim 14,wherein said non-adhering material comprises teflon, titanium or gold.16. The device of claim 15, wherein the means of controlling output ofheat conducted to said tissues comprises a conductive material incontact with said biocompatible material, said conductive materialhaving a thermal history such that application of radiofrequency energyto the conductive material generates an estimable amount of heat. 17.The device of claim 16, wherein said conductive material is a metalwire, a metal particle, a ferromagnetic material, a paramagneticmaterial, a conducting polymer, an ionic molecule, a polar molecule or aconducting microsphere.
 18. The device of claim 16, wherein saidconductive material is an energy-absorbing material, saidenergy-absorbing material comprising conducting polystyrene microbeads,a colloidal metal, a conducting polymer, a strongly ionic molecule or astrongly polar molecule.
 19. The device of claim 1, wherein said devicecomprises an endoscope.
 20. A method for performing an anastomosisbetween at least two tissues comprising the steps of: positioning thedevice of claim 1 around the tissues, said tissues simultaneously incontact with the biocompatible material of said device and with eachother; applying a radiofrequency-induced oscillating magnetic field tothe biocompatible material to generate heat within said material andsaid tissues such that the heating adheres the biocompatible material tothe tissue or adheres the tissues to each other, thereby anastomosingthe tissues.
 21. The method of claim 22, wherein adherence of thebiocompatible material to said tissues or adherence of said tissuesresults from molecular changes in the biocompatible material and in thetissues.